The present invention relates to a feed for prevention and treatment of animal coccidiosis, a coccidiostat, and a method for preventing or treating coccidiosis by supplying an animal with this feed or coccidiostat.
Coccidiosis of poultry such as chicken, turkey, quail and guinea fowl, domestic animals such as rabbit, cow, sheep, goat and pig, and pets such as dog and cat is a disease caused by infection with a certain kind of protozoan parasite and it is frequently found worldwide. Coccidiosis is known to be caused by, in chickens, Eimeria tenella, Eimeria acervulina, Eimeria necatrix, Eimeria brunetti, Eimeria maxima, Eimeria mivati, Eimeria mitis, Eimeria precox or Eimeria hagani; while, in turkeys, by Eimeria meleagrimitis, Eimeria adenoides or Eimeria gallopovonis. 
As is apparent from the above description, species of parasitic protozoa belonging to the genus Eimeria differ between chicken and turkey. The parasitization of protozoa of the genus Eimeria is host specific. Species parasitic on chicken are not parasitic on another bird or animal, but their life cycles are much in common. Described specifically, when an animal ingests a mature oocyst with food or the like from the external world, the wall of the oocyst is broken down inside the gizzard and 4 sporocysts are liberated from one oocyst. These sporocysts are carried to the intestine, at which 2 sporozites are discharged from one sporocyst by the action of an enzyme. These two sporozoites invade the intestinal mucosa cell. By repetition of fission, sporozites each becomes a schizont embracing several to several hundreds merozites in 1 or 2 days. These merozites are released from the broken cell membrane of the schizont and penetrate through the cell of the intestinal membrane. Most of the merozites undergo sexual reproduction into microgametos (male) and macrogametos (female). They are joined and fertilized into oocysts, which are excreted into feces, dropping from the intestinal mucosa. At the time when the oocysts are discharged from the body, they are still immature and not infectious, but in several days, they become mature oocysts equipped with infectiousness. The above-described life cycle is thereafter repeated.
Animals infected with the coccidiosis-causing protozoa belonging to the genus Eimeria show symptoms such as diarrhea or bloody stool. Delay in treatment or serious symptom happens to cause death which is not so rare. Animals even escaped from the death suffer depressed growth. Coccidiosis is therefore one of the animal diseases causing a markedly serious damage and has presented a serious problem particularly for poultry raising farmers who treat a large number of domestic birds.
Upon prevention or treatment of animal coccidiosis, antibiotics (polyether antibiotics such as salinomycin), chemotherapeutics including synthetic antibacterials (such as sulfa preparation), and biological preparations such as vaccine have conventionally be employed mainly. Antibiotics and chemotherapeutics are however accompanied with such problems as emergence of side effects and deterioration of effects due to drug resistance. Vaccine, on the other hand, can be used not for treatment but only for prevention of the disease. In addition to the above-described problems, when the meat or egg of the animal to which such a drug has been administered is taken as a food, the drug residues in the animal body transfer to the human body. A severe limitation must therefore be imposed on the using amount or administration term of the drug.
There is accordingly a demand for a preventive or mitigating preparation of coccidiosis which is free of the above-described problems of an antibiotic, synthetic antibacterial or vaccine, has high safety and has an excellent anticoccidial effect. In Japanese Patent Application Laid-Open No. Hei 8-231410, proposed is a coccidiosis mitigating preparation comprising as an effective ingredient a cashew nut shell oil and/or an anacardic acid, a main component of the cashew nut shell oil. The cashew nut shell oil or anacardic acid is an oil or compound available from a cashew nut shell so that it has excellent characteristics, for example, it has high safety, is free of side effects which occur in the antibiotic or synthetic antibacterial, and furthermore, is free of a deterioration in effects due to drug resistance. A further improvement in the anticoccidial effect is however required in order to prevent or treat coccidiosis more effectively.
An object of the present invention is to provide a coccidiostat which has high safety, is free of problems such as side effects, is free of a decline in effects due to drug resistance and therefore exhibits high preventive and curative effects against coccidiosis; an animal feed containing it, and a method for preventing or treating animal coccidiosis by using the coccidiostat or the feed.
As a result of extensive investigation, the present inventors have found that the use of at least one substance selected from organic zinc compounds, betaines and microorganisms of the genus Bacillus in combination with the above-described cashew nut shell oil and/or an anacardic acid which has been reported to have an ameliorating effect of coccidiosis brings about an improved effect for the prevention or treatment of coccidiosis. Based on such a finding, the present invention has been completed.
The present invention therefore provides a feed for the prevention and/or treatment of coccidiosis, which comprises, together with a cashew nut shell oil and/or an anacardic acid, at least one substance selected from organic zinc compounds, betaines and microorganisms of the genus Bacillus as an effective ingredient.
The present invention also provides a coccidiostat which comprises, together with a cashew nut shell oil and/or an anacardic acid, at least one substance selected from organic zinc compounds, betaines and microorganisms of the genus Bacillus as an effective ingredient.
The present invention further provides a method for preventing or treating animal coccidiosis, which comprises administering the above-described feed or coccidiostat to an animal.
The present invention will hereinafter be described more specifically.
The cashew nut shell oil usable in the present invention is an oil (liquid) contained in the shell of the seed of a cashew nut tree (Anacardiumu occidentale L.). Its preparation process is not particularly limited. As a process for preparing the cashew nut shell oil, known are, for example, a process of heating the shell separated from a cashew nut in the absence or presence of a small amount of a cashew nut shell oil to collect its oil; and a process of extracting the oil from the shell separated from a cashew nut by using an organic solvent (such as hydrocarbon solvent, ketone, alcohol or ester). In the present invention, a cashew nut oil prepared by either one of the above-described processes or a commercially available one, or a mixture thereof may be used.
The cashew nut shell oil contains cardanol, cardol, methylcardol and anacardic acids. In the present invention, anacardic acids separated and collected from the cashew nut shell oil may be used instead of the cashew nut shell oil or they may be used in combination. Anacardic acids are available by eluting the cashew nut shell oil, which has been obtained by extraction of the cashew nut shell with an organic solvent, through chromatography on a silica gel column using a solvent of n-hexane, ethyl acetate and acetic acid mixed at varied ratios (Japanese Patent Application Laid-Open No. Hei 3-240721, Japanese Patent Application Laid-Open No. Hei 3-240716, or the like).
As the organic zinc compound, those taking part in the enzymatic reaction or immune function in vivo can be used. Examples include compounds having an amino acid and zinc bonded therein and compounds having a peptide and zinc bonded therein. These organic zinc compounds may be used either singly or in combination. Specific examples of the organic zinc compound usable in the present invention include zinc-amino acid complex (xe2x80x9cAvaila-Znxe2x80x9d, trade name; product of Zinpro Co.), zinc methionine, and a zinc methionine-zinc lysine mixture (xe2x80x9cZinPlexxe2x80x9d, trade name; product of Zinpro Co.).
The term xe2x80x9cbetainexe2x80x9d is a generic name of an internal salt having, in one molecule thereof, quaternary ammonium as a cation and in addition, an anion of an acid, particularly a carboxylic acid. As the betaine usable in the present invention, any one of such internal salts can be used. Among them, glycine betaine is preferably employed. Glycine betaine is also called lysine, oxyneurine, trimethylglycine or trimethylglycocol and it exists abundantly in many plants such as sugar radish and cotton seed. Glycine betaine separated and purified from the treacle of sucrose is ordinarily used.
Although no particular limitation is imposed on the nature of the microorganism of the genus Bacillus, Bacillus subtilis is preferably used.
In the present invention, it is possible to use, together with the cashew nut shell oil and/or anacardic acid, only one, any two or all three of the organic zinc compound, betaine and microorganism of the genus Bacillus. Among these, use, together with the cashew nut shell oil and/or anacardic acid, of only the microorganism of the genus Bacillus, or of the microorganism of the genus Bacillus and the organic zinc compound and/or betaine in combination tends to bring about a higher anticoccidial effect, with the combined use of the organic zinc compound, betaine and microorganism of the genus Bacillus being more effective.
The feed of the present invention can be obtained by adding, to a basal diet, at least one substance selected from organic zinc compounds, betaines and microorganisms of the genus Bacillus in addition to a cashew nut shell oil and/or an anacardic acid
The content of each of the cashew nut shell oil and/or anacardic acid and at least one substance selected from organic zinc compounds, betaines and microorganisms of the genus Bacillus differs with the kind, age (month) and symptoms of the animal to be fed. From the viewpoint of an anticoccidial effect and liking of animals, it is preferred to add, based on 1000 g of a basal diet (feed prior to the addition of such components), the cashew nut shell oil and/or anacardic acid in an amount of 0.01 to 10 g (total of the cashew nut shell oil and anacardic acid when both are incorporated), particularly 1 to 5 g, the organic zinc compound in an amount of 0.005 to 0.2 g, particularly 0.02 to 0.1 g, the betaine in an amount of 0.1 to 10 g, particularly 0.2 to 1 g, the microorganism of the genus Bacillus in an amount of 107 to 1012, particularly 108 to 1010.
The composition of the feed of the present invention will next be described more specifically.
Preferred as the feed of the present invention are:
(i) a feed containing the organic zinc compound in an amount of 0.005 to 0.2 g, particularly 0.02 to 0.1 g in terms of Zn,
(ii) a feed containing the betaine in an amount of 0.1 to 10 g, particularly 0.2 to 1 g,
(iii) a feed containing the microorganism of the genus Bacillus in an amount of 107 to 1012, particularly 108 to 1010,
(iv) a feed containing the organic zinc compound in an amount of 0.05 to 0.2 g, particularly 0.02 to 0.1 g in terms of Zn, and the betaine in an amount of 0.1 to 10, particularly 0.2 to 1 g,
(v) a feed containing the organic zinc compound in an amount of 0.005 to 0.2 g, particularly 0.02 to 0.1 g in terms of Zn, and the microorganism of the genus Bacillus in an amount of 107 to 1012, particularly 108 to 1010,
(vi) a feed containing the betaine in an amount of 0.1 to 10 g, particularly 0.2 to 1 g and the microorganism of the genus Bacillus in an amount of 107 to 1012, particularly 108 to 1010, and
(vii) a feed containing the organic zinc compound in an amount of 0.005 to 0.2 g, particularly 0.02 to 0.1 g in terms of Zn, the betaine in an amount of 0.1 to 10 g, particularly 0.2 to 1 g, and the microorganism of the genus Bacillus in an amount of 107 to 1012, particularly 108 to 1010, in addition to the cashed nut shell oil and/or anacardic acid in an amount of 0.01 to 10 g, particularly 1 to 5 g, each based on 1000 g of the basal diet.
Among them, the feeds of (iii), (v) and (vii) containing the microorganism of the genus Bacillus, particularly the feeds of (v) and (vii) have a higher anticoccidial effect. Above all, the feed of (vii) containing, in addition to the cashew nut shell oil and/or anacardic acid, three of the organic zinc compound, betaine and microorganism of the genus Bacillus in the above-described predetermined amounts, respectively exhibits a markedly high anticoccidial effect.
There is no particular limitation imposed on the kind or amount of the components contained in the basal diet insofar as they are conventionally fed to animals. For example, corn, corn powder, milo, soybean meal, oats, wheat short, wheat crude powder, alfalfa, clover, defatted rice bran, fish meal, yeast, treacle, meat piece, bone meal, calcium carbonate, calcium diphosphate, yellow grease, vitamins and/or minerals may be added as needed.
The coccidiostat according to the present invention is available by mixing, with the cashew nut shell oil and/or anacardic acid, at least one substance selected from organic zinc compounds, betaines and microorganisms of the genus Bacillus.
An amount of each of the components of the coccidiostat of the present invention can be adjusted, depending on the kind, age (month) or symptoms of the animal to be fed. From the viewpoint of an anticoccidial effect, however, it is preferred to add, relative to 1 g of the cashew nut shell oil and/or anacardic acid (total amount when both of the cashew nut shell oil and anacardic acid are contained),
(i) the organic zinc compound in an amount of 0.005 to 0.1 g, particularly 0.01 to 0.03 g in terms of Zn,
(ii) the betaine in an amount of 0.05 to 5 g, particularly 0.1 to 0.5 g,
(iii) the microorganism of the genus Bacillus in an amount of 107 to 1012, particularly 108 to 1010,
(iv) the organic zinc compound in an amount of 0.005 to 0.1 g, particularly 0.01 to 0.03 g in terms of Zn, and the betaine in an amount of 0.05 to 5 g, particularly 0.1 to 0.5 g,
(v) the organic zinc compound in an amount of 0.005 to 0.1 g, particularly 0.01 to 0.03 g in terms of Zn and the microorganism of the genus Bacillus in an amount of 107 to 1012, particularly 108 to 1010,
(vi) the betaine in an amount of 0.05 to 5 g, particularly 0.1 to 0.5 g and the microorganism of the genus Bacillus in an amount of 107 to 1012, particularly 108 to 1010, or
(vii) the organic zinc compound in an amount of 0.005 to 0.1 g, particularly 0.01 to 0.03 g in terms of Zn, the betaine in an amount of 0.05 to 5 g, particularly 0.1 to 0.5 g, and the microorganism of the genus Bacillus in an amount of 107 to 1012, particularly 108 to 1010.
The coccidiostat according to the present invention may be supplied in any form such as liquid, semisolid (paste or the like) or solid. As a solid form, it can be formulated into powders, granules, tablets, capsules or pills.
The coccidiostat of the present invention can contain various components ordinarily added to a drug such as excipient, filler, binder, disintegrator, sweetener, flavor and spice.
Upon administration of the coccidiostat of the present invention to animals, either oral administration or parenteral administration can be employed, but oral administration is preferred. It may be administered directly to animals or after addition to a feed for animals.
The feed or coccidiostat of the present invention can be used for the prevention or treatment of coccidiosis of not only poultry such as chicken, turkey, quail, geese and guinea fowl, livestock such as pig, cow, sheep, goat and rabbit, and pets such as dog and cat but also any animal known to be infected with coccidiosis.
The amount of the feed or coccidiostat of the present invention to be added to an animal differs with the kind or age (month) of the animal or feeding method thereto. Upon oral administration to a chicken, it is usually recommended to feed the cashew nut shell oil and/or anacardic acid in an amount of about 0.1 to 0.3 g/kg in weight/day; the organic zinc compound in an amount of about 1 to 10 mg/kg in weight/day in terms of Zn; and/or the microorganism of the genus Bacillus in an amount of about 106 to 109/weight kg/day for several days to several tens day.
The feed or coccidiostat of the present invention may be administered to an animal throughout its breeding period or during a certain period. In particular, feeding from just after the birth until 5 weeks of age brings about a high anticoccidial effect.